View source for 1ftq

==STRUCTURES OF GLYCOGEN PHOSPHORYLASE-INHIBITOR COMPLEXES AND THE IMPLICATIONS FOR STRUCTURE-BASED DRUG DESIGN==
<StructureSection load='1ftq' size='340' side='right' caption='[[1ftq]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ftq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FTQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FTQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GL2:3-AMINO-8,9,10-TRIHYDROXY-7-HYDROXYMETHYL-6-OXA-1,3-DIAZA-SPIRO[4.5]DECANE-2,4-DIONE'>GL2</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b4d|1b4d]], [[1ggn|1ggn]], [[1fs4|1fs4]], [[1ftw|1ftw]], [[1fty|1fty]], [[1fu4|1fu4]], [[1fu7|1fu7]], [[1fu8|1fu8]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ftq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ftq OCA], [http://pdbe.org/1ftq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ftq RCSB], [http://www.ebi.ac.uk/pdbsum/1ftq PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PYGM_RABIT PYGM_RABIT]] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ft/1ftq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ftq ConSurf].
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== Publication Abstract from PubMed ==
Glycogen phosphorylase (GP) is currently exploited as a target for inhibition of hepatic glycogenolysis under high glucose conditions. Spirohydantoin of glucopyranose and N-acetyl-beta-D-glucopyranosylamine have been identified as the most potent inhibitors of GP that bind at the catalytic site. Four spirohydantoin and three beta-D-glucopyranosylamine analogs have been designed, synthesized and tested for inhibition of GP in kinetic experiments. Depending on the functional group introduced, the K(i) values varied from 16.5 microM to 1200 microM. In order to rationalize the kinetic results, we determined the crystal structures of the analogs in complex with GP. All the inhibitors bound at the catalytic site of the enzyme, by making direct and water-mediated hydrogen bonds with the protein and by inducing minor movements of the side chains of Asp283 and Asn284, of the 280s loop that blocks access of the substrate glycogen to the catalytic site, and changes in the water structure in the vicinity of the site. The differences observed in the Ki values of the analogs can be interpreted in terms of variations in hydrogen bonding and van der Waals interactions, desolvation effects, ligand conformational entropy, and displacement of water molecules on ligand binding to the catalytic site.

Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase.,Watson KA, Chrysina ED, Tsitsanou KE, Zographos SE, Archontis G, Fleet GW, Oikonomakos NG Proteins. 2005 Dec 1;61(4):966-83. PMID:16222658<ref>PMID:16222658</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ftq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Oryctolagus cuniculus]]
[[Category: Phosphorylase]]
[[Category: Fleet, G W]]
[[Category: Gregoriou, M]]
[[Category: Johnson, L N]]
[[Category: Oikonomakos, N G]]
[[Category: Skamnaki, V T]]
[[Category: Tsitsanou, K E]]
[[Category: Watson, K A]]
[[Category: Zographos, S E]]
[[Category: Catalytic site]]
[[Category: Design]]
[[Category: Glycogen phosphorylase]]
[[Category: Inhibitor complex]]
[[Category: Transferase]]